Methotrexate therapy in primary biliary cirrhosis

We investigated the effect of low-dose oral MTX in a group of patients with PBC.

Sixteen female with a mean age of 51.16 yrs were included in the present study. Criteria for entry into the trial were elevated serum alkaline phosphatase activity, liver biopsy findings diagnostic of or compatible with PBC, and a positive result for serum mitochondrial antibodies with a title > 1/80. Pts. In cirrhotic stage or jaundice were excluded. Ten pts were symptomatic. Pruritus and fatigue were present in 10 pts. At. Inclusion, 7 (43.75%) presented with histological stage 1.6 (37.5%) stage II and 3 (18.75%) stage III (Scheuer). Control liver biopsy was performed on admission and were repeated at 2 years. All pts were treated with MTX 15 mg/wk given orally in three divided doses over 24 hours during 2 years. For statistical the Kruskal Wallis test was used.

Fourteen pts completed 2 years of therapy. Two withdraw from treatment, 1 did so at month 2 due to the worsening of hepatocellular function and development of intense fatigue associated with an elevation of ALT to 30 times over the normal levels and another at month 4 because of interstitial pneumonitis. Pruritus resolved in 5 of the 10 symptomatic patients. All asymptomatic patients remained so during the trial. At the end of the study period, a decline in the following laboratory parameters were observed: Alkaline phosphatase (ALP), from 123 +/- 66 IU/L to 63 +/- 42 IU/L (p = 0.0064); gammaglutamyltransferase (GGT), from 197.3 +/- 121.5 IU/L to 137.2 +/- 56.9 IU/L (p = 0.3352); AST from 47.4 +/- 33 IU/L to 19 +/- 12.4 IU/L (p = 0.0899) and ALT from 54.6 +/- 35 IU/L to 21.12 +/- 5.5 IU/L (p = 0.0771). Liver histology status at the end of MTX therapy improved from baseline in only 3 (18.7%) patients and progression was observed in 8 (50%), to cirrhosis in 4, 3 of them with stage I and another with stage II at the begin of the trial.

Our results do not support the introduction of MTX as monotherapy in the treatment of PBC. The rapid advance off the disease in some patients during the treatment observed in this cohort of pts merits a word of caution.